The term "allergy" means, according to Dorland's Illustrated Medical Dictionary, 24th edition, 1967, "a hypersensitive state acquired through exposure to a particular allergen, re-exposure bringing to light an altered capacity to react". As examples of different allergies may be mentioned asthma, allergic rhinitis, hay fever, and urticaria. A common feature at many types of allergic reactions in humans is an antigen-antibody reaction which leads to the release of pharmacologically active agents (=mediators) i.a. of histamine and SRS-A (=slow reacting substance of anaphylaxis). The mediators thus liberated cause bronchoconstriction, oedema, increased production of mucus, itching, etc. The reaction sequence at an allergic attack may schematically be illustrated as follows: ##STR3##
The kind of exaggerated reaction illustrated above of the organism to allergens (antigens), which may be foreign protein or other substances, is called an anaphylactic reaction.
Although in the following specification emphasis will be placed on bronchial asthma of the exogenous type, which is only one form of allergy, it will be understood that the achievements reached through the present invention will be applied also to other forms of allergy.
In the conventional treatment of asthma, symptoms appearing at step 4 are treated. In particular, the constriction of the bronchi is relieved by administering substances which relieve the bronchial spasm and thus dilate the bronchi. This treatment is, however, usually started only when the asthma attack is under way or already fully developed. It would be desirable to have access to a prophylactic method of treatment which thus could be used to prevent the very outbreak of allergic attacks. This could be achieved by inhibiting the release of mediators appearing in Step 3 in the schema above.
It has been demonstrated that the 1,3-dimethyl derivative of xanthine--theophylline--in some tests is capable of inhibiting the anaphylactic release of histamine, e.g. in basophil leucocytes and in isolated lung tissue.
The object of the present invention is to provide xanthine derivatives which consistently inhibit the allergic reaction in a dosage range where they do not produce "classical" theophylline side effects e.g. CNS-mediated effects and tachycardia. Compounds having a consistent inhibitory effect on the allergic reaction will be effective by various routes of administration as prophylactic antianaphylactic agents in the treatment of allergies including bronchial asthma, without yielding the side effects which may be noted with theophylline drugs conventionally used as bronchospasmolytic agents.